TREM2 triggers microglial density and age-related neuronal loss.
TREM2
aging
microglia
neurodegeneration
oxidative stress
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
23
07
2018
revised:
19
10
2018
accepted:
19
10
2018
pubmed:
15
12
2018
medline:
14
6
2019
entrez:
15
12
2018
Statut:
ppublish
Résumé
The microglial triggering receptor expressed on myeloid cells 2 (TREM2) signals via the activatory membrane adaptor molecule TYROBP. Genetic variants or mutations of TREM2 or TYROBP have been linked to inflammatory neurodegenerative diseases associated with aging. The typical aging process goes along with microglial changes and mild neuronal loss, but the exact contribution of TREM2 is still unclear. Aged TREM2 knock-out mice showed decreased age-related neuronal loss in the substantia nigra and the hippocampus. Transcriptomic analysis of the brains of 24 months old TREM2 knock-out mice revealed 211 differentially expressed genes mostly downregulated and associated with complement activation and oxidative stress response pathways. Consistently, 24 months old TREM2 knock-out mice showed lower transcription of microglial (Aif1 and Tmem119), oxidative stress markers (Inos, Cyba, and Cybb) and complement components (C1qa, C1qb, C1qc, C3, C4b, Itgam, and Itgb2), decreased microglial numbers and expression of the microglial activation marker Cd68, as well as accumulation of oxidized lipids. Cultured microglia of TREM2 knock-out mice showed reduced phagocytosis and oxidative burst. Thus, microglial TREM2 contributes to age-related microglial changes, phagocytic oxidative burst, and loss of neurons with possible detrimental effects during physiological aging.
Identifiants
pubmed: 30548312
doi: 10.1002/glia.23563
pmc: PMC6590266
doi:
Substances chimiques
Membrane Glycoproteins
0
Receptors, Immunologic
0
Trem2 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
539-550Informations de copyright
© 2018 The Authors. Glia published by Wiley Periodicals, Inc.
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